During open heart surgery, cardiopulmonary bypass, by itself, may produce a situation in which clinical deterioration of the patient occurs. The reasons for this are unclear but it is recognized that the longer the duration of perfusion the more likely it is that combined organ systems failure will develop. It is also recognized that the regulation of blood levels of vasoactive substances may be achieved by their removal from blood traversing the pulmonary vascular space. The potential importance of altering the lung's ability to remove vasoactive substances from the blood before and after cardiopulmonary bypass has recently been recognized. Since the lung is known to remove prostaglandin E1 (PGE1), prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) from pulmonary artery blood, it is conceivable that rising circulating levels of these substances, due to removal of the lung from the circulation during cardiopulmonary bypass, may alter the physiology of the capillary endothelium of other organs. Accordingly, our plan is to measure changes in vascular resistance, capillary endothelial permeability, and capillary endothelial extraction of NE, 5-HT, PGE1, and PGF2 alpha by the lungs, kidney, and hind limb of the dog. The capillary permeability-surface area product will be calculated from curves inscribed by isotopes of the above substances and inulin in comparison with a reference substance (albumin) after a single passage through the organ's vascular space. Determinations will be made before, during, and after varying periods of cardiopulmonary bypass. These studies are designed to increase our understanding as to why clinical deterioration may occur after cardiopulmonary bypass and, with the knowledge gained, to design improved methods for providing prolonged cardiopulmonary support.